Flexible granulocyte colony-stimulating factor dosing in ovarian cancer
patients who receive dose-intense taxol therapy
CJ Link , A Bicher, EC Kohn, MC Christian, PA Davis, DO Adamo, E Reed and GA Sarosy
Medical Ovarian Cancer Section, National Cancer Institute, National
Institutes of Health, Bethesda, MD 20892.
As has been reported with other chemotherapeutic agents, evidence is
emerging to suggest that increased taxol dose intensity is associated with
improved therapeutic efficacy. Granulocyte colony-stimulating factor
(G-CSF) effectively protects the bone marrow from taxol-induced neutropenia
and allows for higher taxol dose administration. This report addresses the
optimal use of G-CSF as a supportive agent for dose-intense taxol therapy.
Forty-seven patients were evaluated. Each ovarian cancer patient received
taxol with G-CSF support, with starting doses of 250 mg/m2 per 21 days and
10 micrograms/kg/d, respectively. Five patients were treated with the same
dose of G-CSF for multiple cycles. Forty-two patients were given "flexible"
G-CSF dosing. Instead of reducing taxol dose after a cycle of therapy
complicated by febrile neutropenia (F+N+), the G-CSF dose was increased.
Only after a second episode of F+N+ was the taxol dose reduced. The initial
5 patients who developed F+N+ after taxol (250 mg/m2) and G-CSF (10
micrograms/kg/d) were retreated at the same doses of both drugs;
subsequently, 4 of 5 patients had another episode of F+N+. With flexible
G-CSF dosing, taxol dose intensity could be maintained at the target level
in 34 of 42 patients (81% of the cohort). Sixteen of these patients (38% of
the cohort) would have required taxol dose reductions for F+N+ if flexible
G-CSF dosing had not been used. By increasing the G-CSF dose when
indicated, patients at high risk for recurrence of F+N+, because they had
already experienced one episode, appeared to have a lower risk of
developing a recurrent episode. These data suggest that flexible G-CSF
dosing may have merit and may allow the administration of more dose-
intense taxol. A prospective, randomized, controlled clinical trial of
flexible G-CSF dosing versus fixed-dose G-CSF appears warranted.
Volume 83,
Issue 5,
pp. 1188-1192,
03/01/1994
Copyright © 1994 by The American Society of Hematology
